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A Powerful Toolkit for Synthetic Biology: Over 3.8 Billion Years of Evolution

The combination of evolutionary with engineering principles will enhance synthetic biology. Conversely, synthetic biology has the potential to enrich evolutionary biology by explaining why some adaptive space is empty, on Earth or elsewhere. Synthetic biology, the design and construction of artificial biological systems, substitutes bio-engineering for evolution, which is seen as an obstacle. But because evolution has produced the complexity and diversity of life, it provides a proven toolkit of genetic materials and principles available to synthetic biology. Evolution operates on the population level, with the populations composed of unique individuals that are historical entities. The source of genetic novelty includes mutation, gene regulation, sex, symbiosis, and interspecies gene transfer. At a phenotypic level, variation derives from regulatory control, replication and diversification of components, compartmentalization, sexual selection and speciation, among others. Variation is limited by physical constraints such as diffusion, and chemical constraints such as reaction rates and membrane fluidity. While some of these tools of evolution are currently in use in synthetic biology, all ought to be examined for utility. A hybrid approach of synthetic biology coupled with fine-tuning through evolution is suggested

Rothschild, Lynn J.↗

Lower Limb Venous Compliance is Different Between Men and Women Following 60 Days of Head-Down Bedrest but Is Not Associated with Venoconstriction Dysfunction

Space flight-induced orthostatic intolerance (OI) is more prevalent in female (F) than male (M) astronauts. The mechanisms explaining the higher incidence of OI in F are unclear. We tested the hypothesis that venous compliance would be higher in F more than M following 6 deg head-down bed rest (BR) and would be associated with constrictor dysfunction. Using 2-D ultrasound, dorsal hand (DHV) and dorsal foot (DFV) vein compliances were determined in 24 subjects (10 F, 14 M; 35 +/- 1 yr) by measuring mean diameter response to increasing congestion pressure (0, 20, 30, and 40 mmHg) before and after 60 d of BR. Constrictor function was assessed by intravenous infusions of Ketorolac (KE; 1.5 ig/min) Phenylephrine (PE; 3160 ng/min), and L-NMMA (50 ig/min). The effects of BR between F vs. M and hand vs. foot were determined using mixed-effects linear regression. DFV but not DHV compliance changed in response to BR (p=0.012). Mean DFV increased significantly (0.903 mm to 1.191mm) in F but decreased in M (1.353 mm to 1.154 mm). DFV constrictor response was not different between sexes in response to BR (KE; p=0.647, PE; p=0.717, and L-NMMA; p=0.825). These BR data suggest that the higher incidence of OI in F astronauts may be related to increased lower limb venous compliance, contributing to blood pooling upon standing. Notably, changes to DFV compliance was not accompanied by impaired constrictor function.

Westby, Christian M.↗

True Story of the Moon Rock Heist

In 2002, three NASA Co-op students along with a colleague from the University of Utah stole lunar samples from the Johnson Space Center. Three members of the "gang" removed a 600 pound safe containing lunar, meteorite and Martian samples from Dr. Gibson s laboratory. The thieves offered the samples for sale using the internet. They were arrested by undercover FBI and OIG agents. Three guilty pleas along with a conviction yielded sentences as long as 90 months in federal prison. Two of the thieves went to federal prison and have now been released. One of the thieves told his story to the popular author Ben Mezrich who released the book "Sex on the Moon" in July. Hollywood has "picked-up" the rights to their caper. The stolen lunar samples were not "trash". The loss of 30 years of Dr. Gibson s research records occurred along with contaminating and breaking the chain-of-custody for the lunar samples. The ring-leader has displayed no remorse for his crimes and is currently on the motivational speaker s lecture circuit. Investigators commented "they were the gang, who may have had the highest IQ but the least common sense in history." Previous unreleased information about the crime will be discussed by Dr. Gibson along with information about the forthcoming National Geographic Society s television special on the crime.

Gibson, Everett↗

Satellite-based Estimates of Ambient Air Pollution and Global Variations in Childhood Asthma Prevalence

Background: The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear. Objectives: Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 microm (PM2.5) and nitrogen dioxide (NO2), and modelled estimates of ozone. Methods: We assigned satellite-based estimates of PM2.5 and NO2 at a spatial resolution of 0.1deg × 0.1deg and modeled estimates of ozone at a resolution of 1deg × 1deg to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001-2003). Results: For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM2.5 and NO2 was -0.043 [95% confidence interval (CI): -0.139, 0.053] and 0.017 (95% CI: -0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was -0.116 (95% CI: -0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM2.5 from Phase One to Phase Three was -0.139 (95% CI: -0.347, 0.068). The corresponding association with ozone (per ppbV) was -0.171 (95% CI: -0.275, -0.067). Conclusion: In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.

Air pollution↗

Impact of Gender on Pharmocokinetics of Intranasal Scopolamine

Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS), which is commonly experienced by astronauts during space missions. The bioavailability and pharmacokinetics (PK) were evaluated under IND guidelines. Since information is lacking on the effect of gender on the PK of Scopolamine, we examined gender differences in PK parameters of INSCOP at three dose levels of 0.1, 0.2 and 0.4 mg. Methods: Plasma scopolamine concentrations as a function of time data were collected from twelve normal healthy human subjects (6 male/6 female) who participated in a fully randomized double blind crossover study. The PK parameters were derived using WinNonlin. Covariate analysis of PK profiles was performed using NONMEN and statistically compared using a likelihood ratio test on the difference of objective function value (OFV). Statistical significance for covariate analysis was set at P<0.05(ΔOFV=3.84). Results: No significant difference in PK parameters between male and female subjects was observed with 0.1 and 0.2 mg doses. However, CL and Vd were significantly different between male and female subjects at the 0.4 mg dose. Results from population covariate modeling analysis indicate that a onecompartment PK model with first-order elimination rate offers best fit for describing INSCOP concentration-time profiles. The inclusion of sex as a covariate enhanced the model fitting (ΔOFV=-4.1) owing to the genderdependent CL and Vd differences after the 0.4 mg dose. Conclusion: Statistical modeling of scopolamine concentration-time data suggests gender-dependent pharmacokinetics of scopolamine at the high dose level of 0.4 mg. Clearance of the parent compound was significantly faster and the volume of distribution was significantly higher in males than in females, As a result, including gender as a covariate to the pharmacokinetic model of scopolamine offers the best fit for PK modeling of the drug at dose of 0.4 mg or higher.

Putcha, L.↗

Are Medications Involved in Vision and Intracrancial Pressure Changes Seen in Spaceflight?

The Food and Drug Association Adverse Event Reports (FDA AER) from 2009-2011 were used to create a database from millions of known and suspected medication-related adverse events among the general public. Vision changes, sometimes associated with intracranial pressure changes (VIIP), have been noted in some long duration crewmembers. Changes in vision and blood pressure (which can subsequently affect intracranial pressure) are fairly common side effects of medications. The purpose of this study was to explore the possibility of medication involvement in crew VIIP symptoms. Reports of suspected medication-related adverse events may be filed with the Food and Drug Administration (FDA) by medical professionals or consumers. Quarterly compilations of these reports are available for public download. Adverse Event Reporting System (AERS) reports from 1/1/2009- 6/30/2012 were downloaded and compiled into a searchable database for this study. Reports involving individuals under the age of 18 and older than 65 were excluded from this analysis. Case reports involving chronic diseases such as cancer, diabetes, multiple sclerosis and other serious conditions were also excluded. A scan of the medical literature for medication-related VIIP-like adverse events was used to create a list of suspect medications. These medications, as well as certain medications used frequently by ISS crew, were used to query the database. Queries for use of suspected medications were run, and the nature of the symptoms reported in those cases were tabulated. Symptoms searched in the FDA AERS were chosen to include the typical symptoms noted in crewmembers with VIIP. Vision symptoms searched were: visual acuity reduced, visual impairment, and vitreous floaters. Pressure changes included: abnormal sensation in eye, intracranial pressure increased, intraocular pressure increased, optic neuritis, optic neuropathy, and papilloedema. Limited demographic information is included with the FDA AERS; relevant data were also sorted by age and sex from each report. RESULTS Steroid-containing oral contraceptives had the highest number of reports associated with vision (n=166) and pressure symptoms (n=54). Corticosteroid-containing medications were also high; prednisone, for example, had 137 reports of vision issues and 79 of pressure issues. Pain relievers were also a medication class with vision and pressure-related adverse events reported. Common over-the-counter medications such as acetaminophen, aspirin and ibuprofen each had multiple reports for both vision and pressure symptoms. Antimicrobial medications ciprofloxacin and diflucan were also associated with a number of vision and pressure-related AERS. Unexpectedly, pseudoephedrine and promethazine were mentioned in fewer than 20 reports each over the 3.5 years of data examined. The FDA AERS represents a wealth of data, but there are several limitations to its use. The data are entered by the public or medical professionals, but are not checked for accuracy or completeness and may even be entered multiple times. The causal relationship between a particular adverse event and a particular medication is not tested. The cases represent a broad spectrum of demographics, occupations, and health histories, and thus do not model the astronaut population well. There is no information on the frequency of use of a medication for comparison purposes; it is not possible to assign a rate for any particular adverse event. Nonetheless, there are compelling trends. Use of corticosteroid-containing medications, pain relievers (even over-the-counter), and oral contraceptives were associated with higher numbers of vision- or intracranial pressure-related adverse events. In general, there were more vision problems than pressure problems reported. Certain medications that were once suspected of playing a role in the crew VIIP syndrome, namely pseudoephedrine and promethazine, were found to have extremely low numbers of VIIP-like AERS in the FDA data. However, crew use of corticosteroid-containing medications and pain relievers may warrant additional investigation

Faust, K. M.↗

Men and Women in Space: Bone Loss and Kidney Stone Risk after Long-Duration Space Flight

Bone loss on Earth is more prevalent in women than men, leading to the assumption that women may be at greater risk from bone loss during flight. Until recently, the number of women having flown long-duration missions was too small to allow any type of statistical analysis. We report here data from 42 astronauts on long-duration missions to the International Space Station, 33 men and 9 women. Bone mineral density (dual-energy X-ray absorptiometry), bone biochemistry (from blood and urine samples), and renal stone risk factors were evaluated before and after flight. Data were analyzed in two groups, based on available resistance exercise equipment. The response of bone mineral density to flight was the same for men and women, and the typical decrease in bone mineral density (whole body and/or regional) after flight was not observed for either sex for those using an Advanced Resistive Exercise Device. Bone biochemistry, specifically markers of formation and resorption, generally responded similarly in male and female astronauts. The response of urinary supersaturation risk to space flight was not significantly different between men and women, although risks were typically increased after flight in both groups and risks were generally greater in men than in women before and after flight. Overall, the bone and renal stone responses of men and women to space flight were not different.

Smith, Scott M.↗

Data Mining of Historical Human Data to Assess the Risk of Injury due to Dynamic Loads

The NASA Occupant Protection Group is charged with ensuring crewmembers are protected during all dynamic phases of spaceflight. Previous work with outside experts has led to the development of a definition of acceptable risk (DAR) for space capsule vehicles. The DAR defines allowable probability rates for various categories of injuries. An important question is how to validate these probabilities for a given vehicle. One approach is to impact test human volunteers under projected nominal landing loads. The main drawback is the large number of subject tests required to attain a reasonable level of confidence that the injury probability rates would meet those outlined in the DAR. An alternative is to mine existing databases containing human responses to impact. Testing an anthropomorphic test device (ATD) at the same human‐exposure levels could yield a range of ATD responses that would meet DAR. As one aspect of future vehicle validation, the ATD could be tested in the vehicle's seat and suit configuration at nominal landing loads and compared with the ATD responses supported by the human data set. This approach could reduce the number of human‐volunteer tests NASA would need to conduct to validate that a vehicle meets occupant protection standards. METHODS: The U.S. Air Force has recorded hundreds of human responses to frontal, lateral, and spinal impacts at many acceleration levels and pulse durations. All of this data are stored on the Collaborative Biomechanics Data Network (CBDN), which is maintained by the Wright Patterson Air Force Base (WPAFB). The test device for human occupant restraint (THOR) ATD was impact tested on WPAFB's horizontal impulse accelerator (HIA) matching human‐volunteer exposures on the HIA to 5 frontal and 3 spinal loading conditions. No human injuries occurred as a result of these impact conditions. Peak THOR response variables for neck axial tension and compression, and thoracic‐spine axial compression were collected. Maximal chest deflection was determined from motion capture video of the impact test. HIC‐ 15 and BRIC were calculated from head acceleration responses. Given the number of human subjects for each test condition a confidence interval of injury probability will be obtained. RESULTS: Results will be discussed in terms of injury‐risk probability estimates based on the human data set evaluated. Also, gaps in the data set will be identified. These gaps could be one of two types. One is areas where additional THOR testing would increase the comparable human data set, thereby improving confidence in the injury probability rate. The other is where additional human testing would assist in obtaining information on other acceleration levels or directions. DISCUSSION: The historical human data showed validity of the THOR ATD for supplemental testing. The historical human data are limited in scope, however. Further data are needed to characterize the effects of sex, age, anthropometry, and deconditioning due to spaceflight on risk of injury

Wells, Jesica↗

Assessing the Risk of Crew Injury Due to Dynamic Loads During Spaceflight

Spaceflight requires tremendous amounts of energy to achieve Earth orbit and to attain escape velocity for interplanetary missions. Although the majority of the energy is managed in such a way as to limit the accelerations on the crew, several mission phases may result in crew exposure to dynamic loads. In the automotive industry, risk of serious injury can be tolerated because the probability of a crash is remote each time a person enters a vehicle, resulting in a low total risk of injury. For spaceflight, the level of acceptable injury risk must be lower to achieve a low total risk of injury because the dynamic loads are expected on each flight. To mitigate the risk of injury due to dynamic loads, the NASA Human Research Program has developed a research plan to inform the knowledge gaps and develop relevant tools for assessing injury risk. The risk of injury due to dynamic loads can be further subdivided into extrinsic and intrinsic risk factors. Extrinsic risk factors include the vehicle dynamic profile, seat and restraint design, and spacesuit design. Human tolerance to loads varies considerably depending on the direction, amplitude, and rise-time of acceleration therefore the orientation of the body to the dynamic vector is critical to determining crew risk of injury. Although a particular vehicle dynamic profile may be safe for a particular design, the seat, restraint, and suit designs can affect the risk of injury due to localized effects. In addition, characteristics intrinsic to the crewmember may also contribute to the risk of injury, such as crewmember sex, age, anthropometry, and deconditioning due to spaceflight, and each astronaut may have a different risk profile because of these factors. The purpose of the research plan is to address any knowledge gaps in the risk factors to mitigate injury risk. Methods for assessing injury risk have been well documented in other analogous industries and include human volunteer testing, human exposure to dynamic environments, post-mortem human subject (PMHS) testing, animal testing, anthropomorphic test devices (ATD), dynamic models of the human, numerical models of ATDs, and numerical models of the human. Each has inherent strengths and limitations. For example, human volunteer testing is advantageous because a population can be selected that is similar to the astronaut corps; however, because of the inherent ethical limitations, only sub-injurious conditions can be tested. PMHSs can be tested in a variety of conditions including injurious levels, but the responses are not completely analogous to living human subjects. In addition, it is exceedingly difficult to select a PMHS population that is similar to the astronaut corps. ATDs are currently widely used in the automotive industry and military because they are highly repeatable and durable. Unfortunately, because they are mechanical models of the human body, the biofidelity of the responses are limited to dynamic conditions used to validate the ATD. Numerical models of the ATD, in addition to the strengths and limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional uncertainty. Dynamic models are simple and easy to use, but do not account for localized effects of the seat and suit. Finally, numerical models of the human have the potential to have the most advantages; however, the current models are not validated for the conditions expected during spaceflight. To properly assess spaceflight conditions with numerical human models, human data would be needed to optimize the model responses for those conditions. Using the appropriate assessment method with the knowledge gained for each risk factor, an appropriate approach for mitigating the risk of injury due to dynamic loads can be developed ensuring crew safety in future NASA vehicles.

Somers, J. T.↗

High Performance EVA Glove Collaboration: Glove Injury Data Mining Effort

Human hands play a significant role during Extravehicular Activity (EVA) missions and Neutral Buoyancy Lab (NBL) training events, as they are needed for translating and performing tasks in the weightless environment. Because of this high frequency usage, hand and arm related injuries are known to occur during EVA and EVA training in the NBL. The primary objectives of this investigation were to: 1) document all known EVA glove related injuries and circumstances of these incidents, 2) determine likely risk factors, and 3) recommend interventions where possible that could be implemented in the current and future glove designs. METHODS: The investigation focused on the discomforts and injuries of U.S. crewmembers who had worn the pressurized Extravehicular Mobility Unit (EMU) spacesuit and experienced 4000 Series or Phase VI glove related incidents during 1981 to 2010 for either EVA ground training or in-orbit flight. We conducted an observational retrospective case-control investigation using 1) a literature review of known injuries, 2) data mining of crew injury, glove sizing, and hand anthropometry databases, 3) descriptive statistical analyses, and finally 4) statistical risk correlation and predictor analyses to better understand injury prevalence and potential causation. Specific predictor statistical analyses included use of principal component analyses (PCA), multiple logistic regression, and survival analyses (Cox proportional hazards regression). Results of these analyses were computed risk variables in the forms of odds ratios (likelihood of an injury occurring given the magnitude of a risk variable) and hazard ratios (likelihood of time to injury occurrence). Due to the exploratory nature of this investigation, we selected predictor variables significant at p≤0.15. RESULTS: Through 2010, there have been a total of 330 NASA crewmembers, from which 96 crewmembers performed 322 EVAs during 1981-2010, resulting in 50 crewmembers being injured inflight and 44 injured during 11,704 ground EVA training events. Of the 196 glove related injury incidents, 106 related to EVA and 90 to EVA training. Over these 196 incidents, 277 total injuries (126 flight; 151 training) were reported and were then grouped into 23 types of injuries. Of EVA flight injuries, 65% were commonly reported to the hand (in general), metacarpophalangeal (MCP) joint, and finger (not including thumb) with fatigue, abrasion, and paresthesia being the most common injury types (44% of total flight injuries). Training injuries totaled to more than 70% being distributed to the fingernail, MCP joint, and finger crotch with 88% of the specific injuries listed as pain, erythema, and onycholysis. Of these training injuries, when reporting pain or erythema, the most common location was the index finger, but when reporting onycholysis, it was the middle finger. Predictor variables specific to increased risk of onycholysis included: female sex (OR=2.622), older age (OR=1.065), increased duration in hours of the flight or training event (OR=1.570), middle finger length differences in inches between the finger and the EVA glove (OR=7.709), and use of the Phase VI glove (OR=8.535). Differentiation between training and flight and injury reporting during 2002-2004 were significant control variables. For likelihood of time to first onycholysis injury, there was a 24% reduction in rate of reporting for each year increase in age. Also, more experienced crewmembers, based on number of EVA flight or training events completed, were less likely to report an onycholysis injury (3% less for every event). Longer duration events also found reporting rates to occur 2.37 times faster for every hour of length. Crewmembers with larger hand size reported onycholysis 23% faster than those with smaller hand size. Finally, for every 1/10th of an inch increase in difference between the middle finger length and the glove, the rate of reporting increased by 60%. DISCUSSION: One key finding was that the Series 4000 glove had a lower injury risk than the Phase VI, which provides a platform for further evaluation. General interventions that reduce hand overexertion and repetitive use exposure through tool development, procedural changes and shorter exposures may be one mitigation path, but due to the way the training event times were reported, we cannot provide a guideline for a specific event duration change. When the finger length was different from the glove length, the risk of injury increased indicating that the use of larger finger take-ups could be contributing to injury and therefore may not be recommended. Prior to this investigation, there was one previous investigation indicating hand anthropometry may be related to onycholysis. We found different hand anthropometry variables indicated by this investigation as compared to the prior, specifically differences in middle finger length compared to glove finger length, which point more towards a sizing issue than a specific anthropometry issue. Additionally, although this investigation has identified sizing as an issue, the force and environmental-related variables of the EVA glove that could also cause injury were not accounted for.

Reid, C. R.↗

Assessing the Effect of Spaceflight on the Propensity for Astronauts to Develop Disc Herniation

A previous study reported that the instantaneous risk of developing a Herniated Nucleus Pulposus (HNP) was higher in astronauts who had flown at least one mission, as compared with those in the corps who had not yet flown. However, the study only analyzed time to HNP after the first mission (if any) and did not account for the possible effects of multiple missions. While many HNPs occurred well into astronauts' careers or in somecases years after retirement, the higher incidence of HNPs relatively soon after completion of space missions appears to indicate that spaceflight may lead to an increased risk of HNP. In addition, when an HNP occurs after spaceflight, is it related to previous spaceflight exposure? The purpose of this study was to investigate whether multiple missions, sex, age, vehicle landing dynamics, and flight duration affect the risk of developing an HNP usinga competing risks model. The outcome of the study will inform the Human System Risk Board assessment of back pain, inform the risk of injury due to dynamic loads, and update the previous dataset, which contained events up to December 31, 2006.

Feiveson, A.↗

The Integrated Medical Model: A Probabilistic Simulation Model Predicting In-Flight Medical Risks

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

Risk Analysis↗

Initial Incidence of White Matter Hyperintensities on MRI in Astronauts

Introduction: Previous literature has described the increase in white matter hyperintensity (WMH) burden associated with hypobaric exposure in the U-2 and altitude chamber operating personnel. Although astronauts have similar hypobaric exposure pressures to the U2 pilot population, astronauts have far fewer exposures and each exposure would be associated with a much lower level of decompression stress due to rigorous countermeasures to prevent decompression sickness. Therefore, we postulated that the WMH burden in the astronaut population would be less than in U2 pilots. Methods: Twenty-one post-flight de-identified astronaut MRIs (5 mm slice thickness FLAIR sequences) were evaluated for WMH count and volume. The only additional data provided was an age range of the astronauts (43-57) and if they had ever performed an EVA (13 yes, 8 no). Results: WMH count in these 21 astronaut MRI was 21.0 +/- 24.8 (mean+/- SD) and volume was 0.382 +/- 0.602 ml, which was significantly higher than previously published results for the U2 pilots. No significant differences between EVA and no EVA groups existed. Age range of astronaut population is not directly comparable to the U2 population. Discussion: With significantly less frequent (sometimes none) and less stressful hypobaric exposures, yet a much higher incidence of increased WMH, this indicates the possibility of additional mechanisms beyond hypobaric exposure. This increase unlikely to be attributable just to the differences in age between astronauts and U2 pilots. Forward work includes continuing review of post-flight MRI and evaluation of pre to post flight MRI changes if available. Data mining for potential WMH risk factors includes collection of age, sex, spaceflight experience, EVA hours, other hypobaric exposures, hyperoxic exposures, radiation, high performance aircraft experience and past medical history. Finally, neurocognitive and vision/eye results will be evaluated for any evidence of impairment linked to increased WMH.

Norcross, Jason↗

Compiling a Comprehensive EVA Training Dataset for NASA Astronauts

Training for a spacewalk or extravehicular activity (EVA) is considered a hazardous duty for NASA astronauts. This places astronauts at risk for decompression sickness as well as various musculoskeletal disorders from working in the spacesuit. As a result, the operational and research communities over the years have requested access to EVA training data to supplement their studies. The purpose of this paper is to document the comprehensive EVA training data set that was compiled from multiple sources by the Lifetime Surveillance of Astronaut Health (LSAH) epidemiologists to investigate musculoskeletal injuries. The EVA training dataset does not contain any medical data, rather it only documents when EVA training was performed, by whom and other details about the session. The first activities practicing EVA maneuvers in water were performed at the Neutral Buoyancy Simulator (NBS) at the Marshall Spaceflight Center in Huntsville, Alabama. This facility opened in 1967 and was used for EVA training until the early Space Shuttle program days. Although several photographs show astronauts performing EVA training in the NBS, records detailing who performed the training and the frequency of training are unavailable. Paper training records were stored within the NBS after it was designated as a National Historic Landmark in 1985 and closed in 1997, but significant resources would be needed to identify and secure these records, and at this time LSAH has not pursued acquisition of these early training records. Training in the NBS decreased when the Johnson Space Center in Houston, Texas, opened the Weightless Environment Training Facility (WETF) in 1980. Early training records from the WETF consist of 11 hand-written dive logbooks compiled by individual workers that were digitized at the request of LSAH. The WETF was integral in the training for Space Shuttle EVAs until its closure in 1998. The Neutral Buoyancy Laboratory (NBL) at the Sonny Carter Training Facility near JSC opened in March 1997 and is the current site for US EVA training. Other space agencies also have used water to simulate weightlessness and train for EVAs. Russia has a training facility similar to the NBL named the Hydro Lab. The Hydro Lab began operations at the Gagarin Cosmonaut Training Center (GCTC) in 1980 and has been used extensively to the present. Although a majority of training in the Hydro Lab uses the Russian Orlan suit, a small number of sessions have been conducted using a NASA suit. The Japanese Weightlessness Environment Test System (WETS) went into service at the Tsukuba Space Center in 1997 but was closed in 2011 due to extensive earthquake damage. Several sessions were performed using a NASA suit, but these sessions were short and considered "development" runs. LSAH has assembled records from the WETF, NBL and Hydro Lab. Recording of the EVA training data has changed considerably from 1967 to present. The goal of early record keeping was to track use of hardware components, and the person involved was treated as a suited operator, not as a focus of interest. Records from the past two decades are fairly precise with the person, date, suit type and size noted. On occasion the length of the session was listed, but this data is not included on all records. Records were merged from data sources and extensive cleaning of the records was required since the multiple sources frequently overlapped and duplicated records. To date the LSAH EVA training dataset includes over 12,500 EVA training sessions performed by NASA astronauts since 1981. The following variables are included for most records: Name, Sex, Event date, Event name, HUT type, HUT size, Facility, and Estimated run time. For a smaller subset of records, the following variables are available: Actual run time, Time inverted, and the suit components Waist bearing type, Shoulder harness, Shoulder pads, and Teflon inserts. The LSAH dataset is currently the most complete resource for data regarding EVA training sessions performed by NASA astronauts. However, it is not 100 percent complete since the WETS (Japan) and NBS (Marshall) training facility data were not included. This dataset has been compiled by LSAH to study the relationship of EVA training to musculoskeletal injuries but has many other non-medical applications. This dataset can be provided to other groups in order to respond to program and research questions with appropriate board approvals.

Laughlin, M. S.↗

NASA'S Standard Measures During Bed Rest: Adaptations in the Cardiovascular System

Bed rest is a well-accepted analog of space flight that has been used extensively to investigate physiological adaptations in a larger number of subjects in a shorter amount of time than can be studied with space flight and without the confounding effects associated with normal mission operations. However, comparison across studies of different bed rest durations, between sexes, and between various countermeasure protocols have been hampered by dissimilarities in bed rest conditions, measurement protocols, and testing schedules. To address these concerns, NASA instituted standard bed rest conditions and standard measures for all physiological disciplines participating in studies conducted at the Flight Analogs Research Unit (FARU) at the University of Texas-Medical Branch. Investigators for individual studies employed their own targeted study protocols to address specific hypothesis-driven questions, but standard measures tests were conducted within these studies on a non-interference basis to maximize data availability while reducing the need to implement multiple bed rest studies to understand the effects of a specific countermeasure. When possible, bed rest standard measures protocols were similar to tests nominally used for medically-required measures or research protocols conducted before and after Space Shuttle and International Space Station missions. Specifically, bed rest standard measures for the cardiovascular system implemented before, during, and after bed rest at the FARU included plasma volume (carbon monoxide rebreathing), cardiac mass and function (2D, 3D and Doppler echocardiography), and orthostatic tolerance testing (15- or 30-minutes of 80 degree head-up tilt). Results to-date indicate that when countermeasures are not employed, plasma volume decreases and the incidence of presyncope during head-up tilt is more frequent even after short-duration bed rest while reductions in cardiac function and mass are progressive as bed rest duration increases. Additionally, while plasma volume loss can be corrected and cardiac mass can be prevented with properly applied countermeasures, orthostatic tolerance is more difficult to protect when supine exercise is the only countermeasure. Similar results have been observed after space flight. Plasma volume, cardiac chamber volume, and orthostatic tolerance recover relatively quickly with resumption of ambulation and normal activity levels after bed rest but restoration of cardiac mass is prolonged.

Lee, Stuart M. C.↗

The Integrated Medical Model: A Probabilistic Simulation Model for Predicting In-Flight Medical Risks

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

Risk Analysis↗

NASA Human System Risk Assessment Process

NASA utilizes an evidence based system to perform risk assessments for the human system for spaceflight missions. The center of this process is the multi-disciplinary Human System Risk Board (HSRB). The HSRB is chartered from the Chief Health and Medical Officer (OCHMO) at NASA Headquarters. The HSRB reviews all human system risks via an established comprehensive risk and configuration management plan based on a project management approach. The HSRB facilitates the integration of human research (terrestrial and spaceflight), medical operations, occupational surveillance, systems engineering and many other disciplines in a comprehensive review of human system risks. The HSRB considers all factors that influence human risk. These factors include pre-mission considerations such as screening criteria, training, age, sex, and physiological condition. In mission factors such as available countermeasures, mission duration and location and post mission factors such as time to return to baseline (reconditioning), post mission health screening, and available treatments. All of the factors influence the total risk assessment for each human risk. The HSRB performed a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30, where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research and, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit for 6 and 12 months, deep space for 30 days and 1 year, a lunar mission for 1 year, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary two-page assessment representing the state of knowledge/evidence of that risk, available risk mitigations, traceability to the Space Flight Human System Standards (SFHSS) and program requirements, and future work required. These data then can drive coordinated budgets across the Human Research Program, the International Space Station, Crew Health and Safety and Advanced Exploration System budgets to provide the most economical and timely mitigations. The risk assessments were completed for the 6 DRMs and serve as the baseline for which subsequent research and technology development and crew health care portfolios can be assessed. The HSRB reviews each risk at least annually or when new evidence/information is available that adds to the body of evidence. The current status of each risk can be reported to program management for operations, budget reviews and general oversight of the human system risk management program.

Francisco, D.↗

Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

Oxidative Stress↗